c-Jun involvement in vitamin E succinate induced apoptosis of reticuloendotheliosis virus transformed avian lymphoid cells

Qian, Ming; Králová, Jarmila; Yu, Weiping; Bose, Henry R.; Dvořák, Michal; Sanders, Bob G.; Kline, Kimberly

doi:10.1038/sj.onc.1201181

Cited by 56 publications

(54 citation statements)

References 17 publications

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“…Domain I (the functional domain) is essential for the redox activity of VE analogues, which involves the hydroxyl group in position C6 of the chromanol ring structure. Interestingly, a-TOH does not induce apoptosis (Qian et al, 1997;Neuzil et al, 2001c), nor does it when acetylated at C6 (a-TOA) (Neuzil et al, 2001a). However, succinylation in this position makes a-TOH a strong apoptogen (Neuzil et al, 2001c Figure 1 Functional domains in the molecule of VE.…”

Section: Resultsmentioning

confidence: 99%

“…In this regard, recent findings suggest that certain analogues of vitamin E (VE), such as a-tocopheryl succinate (a-TOS), may represent a new class of antineoplastic agents with high selectivity for malignant cells and low toxicity. a-Tocopheryl succinate causes apoptotic death of a variety of neoplastic cell lines (Fariss et al, 1994;Qian et al, 1997;Neuzil et al, 1999;Yamamoto et al, 2000), whereas neither the redox-active a-tocopherol (a-TOH) nor its uncharged ester, a-tocopheryl acetate (a-TOA), is effective (Qian et al, 1997;Neuzil et al, 2001c). Therefore, the proapoptotic activity appears to be a unique feature of a-TOS, and this agent is also effective in vivo, inhibiting the growth of colon (Weber et al, 2002) and melanoma cancers (Malafa et al, 2001), promoting breast cancer dormancy (Malafa and Neitzel, 2000), and suppressing metastasis (Barnett et al, 2002).…”

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confidence: 99%

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Vitamin E analogues as inducers of apoptosis: structure–function relation

et al. 2003

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Recent results show that a-tocopheryl succinate (a-TOS) is a proapoptotic agent with antineoplastic activity. As modifications of the vitamin E (VE) molecule may affect its apoptogenic activity, we tested a number of newly synthesised VE analogues using malignant cell lines. Analogues of a-TOS with lower number of methyl substitutions on the aromatic ring were less active than a-TOS. Replacement of the succinyl group with a maleyl group greatly enhanced the activity, while it was lower for the glutaryl esters. Methylation of the free succinyl carboxyl group on a-TOS and d-TOS completely prevented the apoptogenic activity of the parent compounds. Both Trolox and its succinylated derivative were inactive. a-tocotrienol (a-T3 H) failed to induce apoptosis, while g-T3 H was apoptogenic, and more so when succinylated. Shortening the aliphatic side chain of g-T3 by one isoprenyl unit increased its activity. Neither phytyl nor oleyl succinate caused apoptosis. These findings show that modifications of different functional moieties of the VE molecule can enhance apoptogenic activity. It is hoped that these observations will lead to the synthesis of analogues with even higher apoptogenic and, consequently, antineoplastic efficacy.

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Section: Resultsmentioning

confidence: 99%

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confidence: 99%

Vitamin E analogues as inducers of apoptosis: structure–function relation

et al. 2003

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“…Although the only structural difference between TS and ␣ -T is a succinyl ester moiety, their physicochemical properties are significantly different. TS has various biological activities that are not observed in ␣ -T, such as suppression of the function of transcriptional factor nuclear factor B (NF-B) [2][3][4][5], enhancement of nitric oxide production induced by lipopolysaccharide/interferon-␥ in rat vascular smooth muscle cells [ 6 ], suppression of the growth of various cancer cells [ 7 , 8 ], and induction of apoptosis in various cell lines [9][10][11][12][13][14][15][16][17][18][19][20][21][22]. Because of its higher cytotoxicity on various cancer cells than on normal cells [ 10 , 14 , 15 ], TS has attracted much attention as a new type of anti-cancer drug, and research on apoptosis induced by TS has been developing every year with a view to exploiting its anti-cancer effect.…”

Section: Introductionmentioning

confidence: 99%

Tocopheryl Succinate—Versatile Functions due to Its Unique Physicochemical Properties

Kogure

Fukuzawa

2004

J. Clin. Biochem. Nutr.

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Summary ␣ -Tocopheryl succinate (TS), a succinyl ester of ␣ -tocopherol ( ␣ -T), has no antioxidant activity, but it does have unique physicochemical properties and shows versatile biological functions. The physicochemical properties of TS affect the structure and function of lipid membranes, and the ability to form bilayer vesicles by itself suggests that TS can become a new carrier in the field of drug delivery systems. The ability to induce apoptosis is a most attractive property of TS. Because TS shows higher cytotoxicity on various cancer cells than on normal cells in vitro , prevents tumor growth, and extends survival in vivo , much attention has been paid to TS as a new type of anti-cancer drug. Activation of various signal transduction factors is also a well-known function of TS. In particular, protein kinase C (PKC), which acts in upstream in the signal transduction, is thought to play an important role in the effects of TS. Our theoretical computational study indicates that TS activates PKC by direct interaction with PKC due to its high structural flexibility.

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“…The sustained induction of c-jun has been implicated as a causative signal in various apoptotic pathways [1][2][3][4][5]. We previously reported data suggesting that c-Jun, the protein coded by the c-jun proto-oncogene, is critical to the glucocorticoid-evoked apoptosis of a human leukemia lymphoblast line [6].…”

Section: Introductionmentioning

confidence: 99%

The delayed induction of c-jun in apoptotic human leukemic lymphoblasts is primarily transcriptional

Zhou

Medh

Zhang

et al. 2000

The Journal of Steroid Biochemistry and Molecular Biology

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Because of their ability to induce lymphoid cell apoptosis, glucocorticoids have been used for decades to treat certain human leukemias and lymphomas. Studies presented in this paper complement our previous work demonstrating that sustained induction of the proto-oncogene c-jun plays a crucial role in the glucocorticoid-induced apoptotic pathway in CEM cells, human leukemic lymphoblasts.Results from measurements of c-jun mRNA half-life with RNase protection assays and of transcription by nuclear run-on assays indicate that, in the dexamethasone-sensitive cloned CEM-C7 cells, c-jun is induced at the transcriptional level. Consideration of time-course, however, suggested that this might be a secondary or possibly a delayed primary response. Use of cycloheximide to block protein synthesis strongly induced c-jun mRNA, suggesting that there had been relief from a labile protein repressor of transcription. Comparing the level of induction by cycloheximide with that of dexamethasone indicated that the two did not induce by an identical mechanism. The high induction by cycloheximide obscured simple interpretation of elevated c-jun mRNA levels after concomitant administration of cycloheximide and dexamethasone. This was resolved by nuclear run-on experiments, which showed that the dexamethasone induction of c-jun mRNA in this system does require protein synthesis.

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c-Jun involvement in vitamin E succinate induced apoptosis of reticuloendotheliosis virus transformed avian lymphoid cells

Cited by 56 publications

References 17 publications

Vitamin E analogues as inducers of apoptosis: structure–function relation

Vitamin E analogues as inducers of apoptosis: structure–function relation

Tocopheryl Succinate—Versatile Functions due to Its Unique Physicochemical Properties

The delayed induction of c-jun in apoptotic human leukemic lymphoblasts is primarily transcriptional

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